Reporting Only ‘Unanticipated’ AEs of Trial Drugs Would Reduce IRB Workload, But Would Patient Safety Suffer?

Enrollment in clinical trials is crucial
to continued scientific discovery and
improved patient care. However, public
trust in clinical trials has diminished in
recent years due to a few well-publicized
deaths and serious adverse events (AEs)
that occurred in phase I/II trials. Minimizing
risks of serious injury and death
during clinical research may increase the
willingness of patient-subjects to participate
in clinical trials. This is particularly
relevant since adverse drug reactions account
for more than 100,000 patient
deaths per year in hospitals in the United
States.[1]

While clinical trials identify benefits
and common side effects of drugs, their
practical size limits the likelihood of detecting
all but the most common AEs
prior to drug approval. Similarly, clinical
trials limit the profile of patients who test
new drugs. As a result, more than half of
all new drugs have serious undetected
toxicities at the time of their initial FDA
approval.[2]

FDA outside of the clinical trial setting is
low, and these reports are often of poor
quality. Failure to detect occurrences of
serious AEs with novel cancer agents in
the clinical trial setting may result in continued
use of these agents in ongoing and
future clinical trials without the necessary
insight about the true toxicity profile,
and subsequent clinical trial participants
can be injured or die from these
toxicities.

With improved pharmaco-vigilance
practices, it may be possible to improve
the detection of serious AEs during clinical
trials--before the drug is approved
and widely available.

Role of IRBs
One means of improving AE detection
is through improved Institutional
Review Board (IRB) mechanisms. IRB
oversight of medication safety is an especially
important issue in oncology clinical
trials due to the expected toxicity of
cancer drugs, the large number of cancer
patients who participate in clinical trials,
the high frequency of comorbidity, the
difficulty in distinguishing drug toxicity
from underlying disease in cancer patients,
and the importance of clinical trials
in both clarifying the optimal uses of
novel cancer agents and improving post-
marketing assessments of safety.

Physician investigators routinely report
information on serious AEs through
reports to IRBs, Data Safety Monitoring
Boards (if applicable), and pharmaceutical
sponsors, who submit required safety
reports to the FDA. In fact, one of the
most important ways the IRB safeguards
clinical trial participants is by ensuring
there is an adequate data and safety monitoring
plan related to a study.

Flood of Reported AEs
In the 1990s, drug companies extended
the regulatory requirements issued by the
government and began to require that all
serious AEs of a drug under investigation
be reported to the investigators' local IRB,
including reports from other study sites
and from other studies with the investigational
drug. This led to a flood of paperwork
and adverse event reports--
many of them overlapping--that have
overwhelmed chronically underfunded
IRBs.[3] For example, one large center
reported receiving more than 10,000 reports
per year with only one primary person
available to read and interpret the
reports.